The chemokine receptor CXCR6 and its ligand CXCL16 are expressed in carcinomas and inhibit proliferation (Retracted article. See vol. 71, pg. 1196, 2011)
The chemokine receptor CXCR6 and its ligand CXCL16 are expressed in carcinomas and inhibit proliferation (Retracted article. See vol. 71, pg. 1196, 2011)
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DOI：
10.1158/0008-5472.can-08-0482
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发表时间：
2008-06-15
期刊：
影响因子：
11.2
通讯作者：
Roos, Ed
中科院分区：
文献类型：
--
作者：
Meijer, Joost;Ogink, Janneke;Roos, Ed
趋化因子受体CXCR 6及其配体CXCL 16参与炎症。到目前为止，已知它们分别主要由T细胞和巨噬细胞表达。然而，我们在所有170例人原发性乳腺癌中检测到了这两种蛋白，并且在通过微阵列分析测试的所有8种人乳腺癌细胞系中检测到了相似的水平。通过逆转录-PCR证实表达，并且对于细胞系还通过荧光激活细胞分选分析证实表达。CXCR 6和CXCL 16也在几种小鼠和人乳腺癌、结肠癌和胰腺癌细胞系中检测到。CXCL 16是一种跨膜蛋白，可溶性趋化因子可以从其上裂解掉。跨膜形式存在于癌细胞的表面。令人惊讶的是，CXCR 6或CXCL 16的抑制导致体外以及体内增殖大大增强，表明它们的相互作用抑制增殖。使用抑制性抗体并通过将CXCL 16引入罕见的CXCL 16阴性细胞系来验证这一概念。这种作用是由G蛋白偶联受体CXCR 6介导的，因为它被G（i）蛋白抑制剂百日咳毒素阻断。相反，可溶性CXCL 16趋化因子促进增殖，这也是由CXCR 6介导的，但不是通过G（i）蛋白。值得注意的是，所有乳腺癌都表达CXCR 6和CXCL 16，因为丢失的细胞获得生长优势，并且应该在肿瘤进展期间被选择。这表明在肿瘤形成中有一个未知的重要作用。蛋白酶，可能是巨噬细胞衍生的，可以将抑制性跨膜CXCL 16转化为刺激性趋化因子。
The chemokine receptor CXCR6 and its ligand CXCL16 are involved in inflammation. Thus far, they were known to be expressed mainly by T cells and macrophages, respectively. However, we detected both in all of 170 human primary mammary carcinomas and at similar levels in all 8 human mammary carcinoma cell lines tested by microarray analysis. Expression was confirmed by reverse transcription-PCR and for the cell lines also by fluorescence-activated cell sorting analysis. CXCR6 and CXCL16 were also detected in several mouse and human mammary, colon, and pancreatic carcinoma cell lines. CXCL16 is a transmembrane protein from which the soluble chemokine can be cleaved off. The transmembrane form is present on the surface of the carcinoma cells. Surprisingly, suppression of either CXCR6 or CXCL16 led to greatly enhanced proliferation in vitro as well as in vivo, indicating that their interaction inhibits proliferation. This notion was verified using inhibitory antibodies and by introduction of CXCL16 into a rare CXCL16-negative cell line. The effect was mediated by the G protein-coupled receptor CXCR6 because it was blocked by the G(i) protein inhibitor pertussis toxin. In contrast, the soluble CXCL16 chemokine enhanced proliferation, and this was also mediated by CXCR6 but not via G(i) protein. It is remarkable that both CXCR6 and CXCL16 are expressed by all mammary carcinomas because cells that lose either acquire a growth advantage and should be selected during tumor progression. This suggests an unknown important role in tumor formation. Proteases, possibly macrophage derived, might convert inhibitory transmembrane CXCL16 into the stimulatory chemokine.